Aim Allogeneic hematopoietic stem cell transplantation (HSCT) has curable potential for hematopoietic malignancies through graftversusleukemia (GVL) effects but is often associated with lifethreatening graftversushost disease (GVHD).Donor T cells play an important role in the pathological process of GVHD.In this study, to determinate immunoisolation through encapsulating T cells with biomaterials could be a promising approach to attenuate GVHD.Methods T cells were isolated from spleens of donor C57B1/6 mice by magnetic cell separation and coated by layerbylayer in chitosan and alginate.BALB/c recipient mice were established GVHD mode and leukemia mode.Xenogen IVIS imaging system was used for live animal imaging.Donor BMCs and T cell subsets were analyzed by flow cytometry.Results In this study, we successfully encapsulated T cells of mice in muhilayers of chitosan and alginate.In vitro studies showed that the encapsulation did not change the phenotype of T cells as defined through the following parameters: size, viability, proliferation, antibody binding, cytokine secretion, and cytotoxicity.Mice transplanted with encapsulated allogeneic T cells exhibited less severe acute GVHD and prolonged survival.The mice showed a lower GVHD score, less liver damage, a smaller CDS/CD4 T cell ratio, and a higher number of donor BMderived cells following transplantation with encapsulated donor T cells.When this GVHD model was combined with implantation of A20 lymphoma cells, GVL of encapsulated T cells was not compromised,while GVHD was still suppressed and the mouse survival also prolonged.Conclusion These studies demonstrate that encapsulation of T cells with biodegradable materials could attenuate the severity of GVHD but retaine GVL,which presents a novel and potentially safer and effective approach of allogeneic HSCT for future clinical application.